The objectives are to gain an insight into the nature of the antigenic determinants of myelin and its components, in particular the manner in which the determinants of purified myelin components become modified, changed, or lost as a result of their combination with other myelin components to produce the conformations of native myelin; and to determine whether tolerance is established (and broken) at the level of separate myelin components and/or operates at the level of conformationally intact myelin and myelin subunits. The general design cells for two approaches -- the preparation of antibodies against isolated myelin components, and the study of those antibodies in their interaction with complexes of the components all the way up to fully assembled myelin; and the preparation of antibodies against fully assembled myelin and myelin subfractions, and the study of these antibodies in the interaction with less complex assemblages all the way down to individual isolated components. An in-depth study of antibodies to myelin basic protein (MBP) has already been launched and will be continued; studies of antibodies to proteolipid protein (PLP) and sulfatides will follow. Antibodies to a myelin subfraction designated 80-II-B have already been raised, and will be the first antimyelin antibodies to be studies in depth. Antibodies to purified but unshocked "myelinosomes" also will be investigated since they may approach the type complementary to native myelin surfaces. The sodium-sulfate method of radioimmunoassay will be used to measure anti-MBP antibodies by direct binding with 125I-MBP; binding inhibition and myelin adsorption methods will also be used. A liposome technique will be used to capture antiglycolipid activity; and an adsorption assay will be worked out to measure anti-PLP activity. Serum factors such as MBP-SF, that are cross-reactive with myelin components, will be investigated and measured by inhibition of antibody binding as already worked out for MBP-SF.